Nearly every Claret Sentinel embolic filter placed turned up debris when removed (99%), including thrombus, valve tissue, artery wall and foreign material, reported Susheel Kodali, MD, of New York Presbyterian/Columbia University Medical Center in New York City and colleagues here at the Transcatheter Cardiovascular Therapeutics meeting and online in the Journal of the American College of Cardiology.

But for the primary efficacy endpoint, new lesion volume on MRI scans on days 2 to 7 in brain territories downstream of the device, which covers the left common carotid arteries and the brachiocephalic artery but not the left vertebral artery, was not significantly different than among controls not treated with the filter in place (102.8 versus 178.0 mm3, P=0.33).

And while the 7.3% major adverse cardiac and cerebrovascular event rate at 30 days fell well within the trial's performance goal of 18.3% (P<0.001 for non-inferiority), it wasn't significantly lower than seen among controls (9.9%, P=0.41).

Strokes at 30 days occurred in 5.6% of filter-protected patients and 9.1% of controls, which again was not significant at P=0.25. Nor did neurocognitive function differ between groups.

The trial wasn't powered for clinical outcomes, but "that 9.1% tells us stroke is still a problem with TAVR," Kodali noted at a press conference for the late-breaking clinical trial session.

The captured debris too confirmed "the clear embolic risk during TAVR with frequent embolization of non-thrombotic material (arterial wall in 94% of cases), thus corroborating the fact that more aggressive antithrombotic therapy would not have prevented neurological injury," Azeem Latib, MD, and Matteo Pagnesi, MD, both of the San Raffaele Scientific Institute in Milan, Italy, wrote in an accompanying editorial.

Although the prior CLEAN TAVI trial with an earlier version of the Claret device both failed to find a clinical impact, "in our opinion, it would be inappropriate and unfair to close the book on cerebral protection after this chapter," the editorialists argued.

For one thing, they pointed out, even "the current Sentinel device fully protects only nine out of 28 brain regions, because of the dual blood supply of the posterior circulation," although no device is likely to be able to completely protect the brain regardless of design.

"In considering all these potential pitfalls of a performing a randomized study of cerebral embolic protection during TAVR, the small imaging sample size is probably the main reason the SENTINEL study is negative," they suggested.

The trial included 363 patients at 19 centers getting TAVR with a variety of FDA-approved prostheses who were randomized to one of the following:

A safety group who got the Sentinel device but no imaging, to save money while capturing clinical events

A device group who also had MRI imaging and the comprehensive neurocognitive assessment

A control group who got imaging and neurocognitive testing but no embolic protection device

The study allowed nonstratified use of any TAVR valve, with substantially lower new lesion volume with the newer generation Sapien 3 device compared with Evolut R or Sapien XT. Looking only at the embolic protection effect in the Evolut and XT valve patients, the effect was significant.

However, Kodali noted that patient selection-related device differences could have contributed confounding. And, "these are very small numbers to be making any sort of conclusions about where this will be useful," cautioned press conference discussion panelist Jeffrey Popma, MD, of Beth Israel Deaconess Medical Center in Boston.

Analyses adjusting for baseline lesion volume and for type of TAVR device used, did show a significant difference in new lesion volume favoring the embolic filter in both protected (P=0.025) and all brain territories (P=0.050).

"Indeed, if we pool study-level data from the three randomized trials investigating the Claret cerebral embolic protection device, it would result in a total of 314 patients undergoing TAVR with (n=165) or without (n=149) cerebral embolic protection," the editorialists wrote. "This pooled analysis suggests that the Sentinel double-filter significantly reduces total new lesion volume in protected regions by approximately 100 mm3 of damaged brain, i.e., 8 million neurons and 450 million synapses."

"We are dealing with a potential benefit that cannot be ignored as TAVR shifts to younger and lower-risk patients, where preventing procedure-related cerebral injury remains a significant unmet clinical need with potentially important long-term sequelae," Latib and Pagnesi concluded.

The study did provide the first proof of a link between volume and number of new lesions and neurocognitive decline at 30 days.

And patients may respond to that concept intuitively despite the lack of statistical significance, David Holmes, MD, of the Mayo Clinic in Rochester, Minn., said as a panelist at the press conference. "Nobody is going to do a study to wait 20 years to see if there's dementia. That's not going to happen. So what can do is say this is a surrogate. The surrogate is stuff that goes to your brain can't be good for you. And if it's safe ... undoubtedly I think people will use that as a default strategy."

Kodali agreed. "Stroke can have catastrophic consequences. We're not talking about CK release with filter devices in vein grafts ... For a lot of people it's the safety of the device. We do embolic protection in carotid stenting. There's been no randomized trial showing a benefit of embolic protection in carotid stenting. There are reasons for that. I don't think it's justified to do a randomized trial. We've done analyses and we've proved here now the safety of the procedure. There was no increase in MACE with this procedure."

Nor were there any serious adverse events related to the filter, although total procedure was longer by about 13 minutes and fluoroscopy time by 3 minutes.

The SENTINEL trial was funded by Claret Medical.

Kodali disclosed being a consultant for Edwards Lifesciences.

Coauthors included an employee of Claret Medical and an employee of the medical research organization North American Science Associates.

The editorialists disclosed their center is or has been involved in clinical studies of cerebral embolic protection devices for TAVR developed by Claret Medical, Keystone Heart, and Innovative Cardiovascular Solutions.

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